NM_014290.3:c.33A>G

Variant names:

• chr9-97428498-A-G
• rs1381532
• NM_014290.3:c.33A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014290.3(TDRD7):​c.33A>G​(p.Leu11Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,556 control chromosomes in the GnomAD database, including 197,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21774 hom., cov: 32)
  • Exomes 𝑓: 0.49 (175889 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.52
• Publications: 26 publications found

Genes affected

TDRD7 (HGNC:30831): (tudor domain containing 7) The protein encoded by this gene belongs to the Tudor family of proteins. This protein contains conserved Tudor domains and LOTUS domains. It is a component of RNA granules, which function in RNA processing. Mutations in this gene have been associated with cataract formation in mouse and human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

TDRD7 Gene-Disease associations (from GenCC):

• cataract 36

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 9-97428498-A-G is Benign according to our data. Variant chr9-97428498-A-G is described in ClinVar as Benign. ClinVar VariationId is 260382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014290.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD7	NM_014290.3	MANE Select	c.33A>G	p.Leu11Leu	synonymous	Exon 2 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-15-2435A>G		intron	N/A	NP_001289813.1	Q8NHU6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD7	ENST00000355295.5	TSL:1 MANE Select	c.33A>G	p.Leu11Leu	synonymous	Exon 2 of 17	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.33A>G	p.Leu11Leu	synonymous	Exon 3 of 18	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.33A>G	p.Leu11Leu	synonymous	Exon 2 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80740 AN: 151930 Hom.: 21732 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.523

GnomAD2 exomes AF: 0.508 AC: 127526 AN: 251002 AF XY: 0.499

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.562

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.489 AC: 714018 AN: 1461508 Hom.: 175889 Cov.: 59 AF XY: 0.486 AC XY: 353490 AN XY: 727076

African (AFR) AF: 0.608 AC: 20359 AN: 33462

American (AMR) AF: 0.579 AC: 25865 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12358 AN: 26124

East Asian (EAS) AF: 0.531 AC: 21071 AN: 39696

South Asian (SAS) AF: 0.438 AC: 37764 AN: 86254

European-Finnish (FIN) AF: 0.482 AC: 25767 AN: 53406

Middle Eastern (MID) AF: 0.405 AC: 2325 AN: 5744

European-Non Finnish (NFE) AF: 0.485 AC: 538952 AN: 1111756

Other (OTH) AF: 0.490 AC: 29557 AN: 60374

GnomAD4 genome AF: 0.532 AC: 80834 AN: 152048 Hom.: 21774 Cov.: 32 AF XY: 0.532 AC XY: 39504 AN XY: 74312

African (AFR) AF: 0.612 AC: 25378 AN: 41476

American (AMR) AF: 0.555 AC: 8479 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2897 AN: 5166

South Asian (SAS) AF: 0.437 AC: 2103 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5228 AN: 10558

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33461 AN: 67968

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.501 Hom.: 25105

Bravo AF: 0.540

Asia WGS AF: 0.513 AC: 1784 AN: 3478

EpiCase AF: 0.476

EpiControl AF: 0.480

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Cataract 36 (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.83
DANN	Benign	0.74
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1381532; hg19: chr9-100190780; COSMIC: COSV62428704;